Preoperative Occult Neurodegeneration and Postoperative Delirium

术前隐匿性神经变性和术后谵妄

• 批准号: 10589054
• 负责人: GREGORY CROSBY
• 金额: $ 89.09万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589054
• 关键词: Acceleration; Acute; Address; Age; Age Years; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Amyloidosis; Anesthesia procedures; Biological Markers; Brain; CD14 gene; Cerebrum; Characteristics; Clinical; Cognition; Cognitive; Confusion; Data; Delirium; Dementia; Development; Diagnosis; Distress; Elderly; Future; Glial Fibrillary Acidic Protein; Immune response; Impaired cognition; Impairment; Inflammation; Inflammatory Response; Injury; Lead; Light; Magnetic Resonance Imaging; Measures; Morbidity - disease rate; Nerve Degeneration; Neurobehavioral Manifestations; Neurobiology; Neurodegenerative Disorders; Neuropathogenesis; Observational Study; Operative Surgical Procedures; Outcome; Pathogenicity; Pathology; Patients; Perioperative Care; Plan B; Plasma; Positron-Emission Tomography; Postoperative Period; Predisposition; Prevalence; Principal Investigator; Procedures; Proteome; Proxy; Recovery of Function; Research; Risk Assessment; Risk Factors; Severities; Spinal Puncture; Spine surgery; Surgical complication; Symptoms; Syndrome; Tauopathies; Testing; Time; UCHL1 gene; Validation; Work; axon injury; blood-based biomarker; brain magnetic resonance imaging; cerebral atrophy; cost; human old age (65+); improved; improved outcome; innovation; monocyte; nerve injury; neural; neurofilament; neuroinflammation; neuropathology; novel; older patient; postoperative delirium; primary outcome; programs; prospective; risk prediction; secondary outcome; surgical risk; systemic inflammatory response; tau Proteins; transcriptome

Program Director/Principal Investigator (Last, First, Middle): Crosby, Gregory J. ABSTRACT Delirium is the most common complication of surgery and anesthesia in older patients, afflicting 15-60% of those having non-cardiac procedures. This is a major clinical problem because nearly 40% of surgical procedures are performed on older patients and delirium is associated with serious morbidity, including accelerated decline to dementia. Still, the cause of postoperative delirium is uncertain and its neuropathogenesis is unknown. Cerebral neurodegenerative pathology characteristic of Alzheimer’s disease and related disorders is common even in cognitively normal older people, and by the time even mild symptoms develop is pronounced. We hypothesize that this preexisting burden of occult cerebral neurodegeneration accounts for enhanced vulnerability to postoperative delirium (Aim 1), augments surgery- and delirium-induced cerebral injury (Aim 2), and fuels surgery- and delirium-induced inflammation, which aggravates neural injury and increases neurodegeneration (Aim 3). We will test these hypotheses in a longitudinal prospective observational study of older surgical patients evaluated preoperatively for cognitive impairment and followed postoperatively for delirium and longer-term cognitive decline, with neurodegeneration and neural injury defined by ultrasensitive plasma biomarkers and cerebral MR imaging. This project is innovative because it addresses the key question of whether surgery and anesthesia produce delirium and persistent cognitive decline de novo or by unmasking or exacerbating a cerebral precondition and is significant because of the magnitude of the clinical problems (neurodegenerative disease, delirium), practicality of the approach (blood- based biomarkers), and potential to improve the outcomes of vulnerable older surgical patients. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page

项目主管/首席研究员（最后、第一、中）：Crosby, Gregory J。